Biomarkers for gastrointestinal adverse events related to thiopurine therapy

doi:10.3748/wjg.v27.i38.6348

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Oct 14, 2021 (publication date) through Feb 25, 2026

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World Journal of Gastroenterology

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1007-9327

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World J Gastroenterol. Oct 14, 2021; 27(38): 6348-6356
Published online Oct 14, 2021. doi: 10.3748/wjg.v27.i38.6348

Biomarkers for gastrointestinal adverse events related to thiopurine therapy

Giulia Zudeh, Raffaella Franca, Gabriele Stocco, Giuliana Decorti

Giulia Zudeh, Gabriele Stocco, Department of Life Sciences, University of Trieste, Trieste 34127, Italy

Raffaella Franca, Giuliana Decorti, Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste 34149, Italy

Giuliana Decorti, Institute for Maternal and Child Health I.R.C.C.S Burlo Garofolo, Trieste 34137, Italy

Author contributions: Zudeh G and Franca R wrote, revised, and edited the manuscript; Stocco G conceptualized, edited, and revised the manuscript; Decorti G conceptualized, wrote, revised, edited, and supervised the manuscript; all authors read and approved the final manuscript.

Conflict-of-interest statement: All authors declare no conflicts of interest for this manuscript.

Corresponding author: Gabriele Stocco, PhD, Associate Professor, Department of Life Sciences, University of Trieste, Via Fleming 22, Trieste 34127, Italy. stoccog@units.it

Received: March 12, 2021
Peer-review started: March 12, 2021
First decision: April 17, 2021
Revised: April 29, 2021
Accepted: September 3, 2021
Article in press: September 3, 2021
Published online: October 14, 2021
Processing time: 213 Days and 18.1 Hours

Abstract

Thiopurines are immunomodulators used in the treatment of acute lymphoblastic leukemia and inflammatory bowel diseases. Adverse reactions to these agents are one of the main causes of treatment discontinuation or interruption. Myelosuppression is the most frequent adverse effect; however, approximately 5%-20% of patients develop gastrointestinal toxicity. The identification of biomarkers able to prevent and/or monitor these adverse reactions would be useful for clinicians for the proactive management of long-term thiopurine therapy. In this editorial, we discuss evidence supporting the use of PACSIN2, RAC1, and ITPA genes, in addition to TPMT and NUDT15, as possible biomarkers for thiopurine-related gastrointestinal toxicity.

Keywords: Thiopurines; Gastrointestinal adverse effects; Biomarkers; PACSIN2; RAC1; ITPA

Core Tip: Adverse reactions to thiopurines are one of the main causes of treatment discontinuation or interruption. In addition to myelosuppression, approximately 5–20% of patients develop gastrointestinal toxicity; the identification of biomarkers to prevent and/or monitor these adverse reactions is important for the proactive management of long-term thiopurine therapy. In this editorial, we discuss evidence supporting the use of PACSIN2, RAC1, and ITPA genes, in addition to TPMT and NUDT15, as possible biomarkers for thiopurine-related gastrointestinal toxicity.